Breast NeoplasmsPhase 1NCT01265927
A Study Inhibiting Telomerase to Reverse Trastuzumab Resistance in HER2+ Breast Cancer
A Phase 1 study testing GRN163L in combination with trastuzumab in people with Breast Neoplasms, run by Indiana University at 1 site in United States.
Trial summary
A study to evaluate safety and biologic effects of giving GRN163L in combination with trastuzumab in patients diagnosed with HER2+ metastatic breast cancer that is resistant to therapy with trastuzumab. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Neoplasms
- What is being tested?
- GRN163L in combination with trastuzumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2011to Oct 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males or females 18 years or older at the time of consent.
- ECOG performance status of 0-2 within 21 days of study registration.
- Histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease. NOTE: locally recurrent disease must not be amenable to surgery or radiation with curative intent.
- Measurable or evaluable disease according to RECIST v1.1 within 35 days prior to study registration.
- Disease must be amenable to biopsy (image-guided or via direct visualization of superficial lesions) with minimal risk to the patient. NOTE: Patients with disease limited to the lung and/or pleura are excluded.
- Disease must be HER2+ as defined by IHC 3+ or FISH ratio > 2.0.
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- Resistant to trastuzumab as defined as (1) progression within 12 months of completing adjuvant/neoadjuvant trastuzumab or (2) progression on trastuzumab administered for metastatic disease.
- Prior treatment with lapatinib or investigational HER2 targeted therapies is allowed but not required. There are no limits on the number of regimens or other prior anti-HER2 therapies patients have received.
- LVEF ≥ Lower Limit of Normal based on MUGA or ECHO within 35 days prior to study registration
- Females of childbearing potential and males must be willing to use an effective method of contraception from the time consent is signed until 6 months after treatment discontinuation. Methods of contraception include hormonal birth control (oral contraceptives, patch, injection, vaginal ring or implant), two barrier methods of birth control, abstinence and/or other methods as determined by the treating physician.
- Females of childbearing potential must have a negative pregnancy test within 14 days prior to registration for protocol therapy.
- NOTE: Females are considered of child bearing potential unless they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal (> 12 months since last menses).
- Laboratory values must be obtained within 21 days of study registration:
- Absolute neutrophil count (ANC) ≥ 1.5 K/mm3
- Platelets ≥ 100 K/mm3
- Hemoglobin (Hgb) ≥ 9.0 g/dL (may be transfused)
- Serum creatinine < 3.0 mg/dL
- Total Bilirubin ≤ 1.5 x ULN
- AST/SGOT ≤ 2.5 x ULN. If liver metastases is present, AST ≤ 5 x ULN
- ALT, SGPT ≤ 2.5 x ULN. If liver metastases is present, ALT ≤ 5 x ULN
Who cannot join
- No Investigational therapy within 4 weeks of study registration
- No hormonal therapy within 2 weeks of study registration
- No cytotoxic chemotherapy within 2 weeks of study registration.
- No prior treatment with GRN163L
- No prior history of severe reaction to trastuzumab, as determined by the treating physician.
- No history of clinically significant cardiac dysfunction, including:
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- Current uncontrolled hypertension (systolic >150 mmHg and/or diastolic >100 mmHg), or unstable angina History of symptomatic CHF (Grade >3 by NCI CTCAE or Class >II by NYHA criteria [see Appendix IV]) or serious cardiac arrhythmia requiring treatment within 12 months of study registration, with the exceptions of atrial fibrillation and paroxysmal supraventricular tachycardia History of myocardial infarction within 6 months of study registration
- No history of cerebrovascular accident within 12 months of study registration
- No active CNS metastases. Patients with previously treated CNS metastases who do not require chronic steroids or anticonvulsants are eligible.
- Prior radiation therapy must not have involved > 25% of bone marrow due to potential myelosuppression with GRN163L. See bone marrow chart in Appendix III
- NOTE: Radiation therapy within 2 weeks of study registration is not allowed.
- Females must not be breastfeeding.
- No clinically significant active infection, as determined by the treating physician
Trial locations and contacts
1 site in 1 country.
United States1 site
Indiana University Simon Cancer Center
Indianapolis, Indiana, 46202
About this study
Official title: A Phase I Study Inhibiting Telomerase to Reverse Trastuzumab Resistance in HER2+ Breast Cancer
A study to evaluate safety and biologic effects of giving GRN163L in combination with trastuzumab in patients diagnosed with HER2+ metastatic breast cancer that is resistant to therapy with trastuzumab.
- Conditions
- Breast Neoplasms
- Being tested
- GRN163L in combination with trastuzumab
- Keywords
- Breast Cancer, Breast Tumors, Cancer of Breast, Cancer of the Breast, Genes, HER-2, Genes, HER2
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GRN163L in combination with trastuzumabDrug
Also called Imetelstat Sodium, Herceptin
GRN163L will be administered in escalating dose cohorts on Day 1 of each 21-day cycle prior to trastuzumab infusion. Trastuzumab will be a administered day 1 of each 21-day cycle after GRN163L. There will be a 30 minute observation period between the end of the GRN163L infusion and the beginning of the trastuzumab infusion.
| Study group | Role | What they receive |
|---|---|---|
| GRN163L + Trastuzumab | Experimental | Not described Receives: Drug: GRN163L in combination with trastuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the dose-limiting toxicity of GRN163L in combination with trastuzumab in patients with refractory HER2+ metastatic disease
Measured: End of Study
Secondary outcomes (5)
Measure the concentration of trastuzumab and GRN163L from blood samples immediately before and after infusion on day 1, weekly during cycle 1, and immediately prior to cycle 2
PK data will be described using means, standard deviations, medians, minimums and maximums.
Measured: Until cycle 2
Tumor biopsy and bone marrow aspirate assayed for telomerase activity prior to treatment and immediately prior to planned cycle 2
Telomerase activity data will be described using means, standard deviations, medians, minimums and maximums.
Measured: Until cycle 2
Flow cytometry to compare cell cycle distribution in tumor and bone marrow prior to treatment and immediately prior to cycle 2.
Marrow (and tumor when sufficient sample is available) will be analyzed via flow cytometry to determine cell distribution. Percentage of cells at each cycle will be described using means, standard deviations, medians, minimums and maximums.
Measured: Until cycle 2
Tumor samples analyzed for activation of HER2 family signaling protein activation (phosphorylation) status prior to treatment and immediately prior to cycle 2.
HER2 family signaling protein activation will be described using means, standard deviations, medians, minimums and maximums.
Measured: Until cycle 2
Determine objective response rate (ORR) and progression free survival (PFS) of GRN163L in combination with trastuzumab in this patient population
Measured: End of Study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2010 (estimated)
- Study startJan 2011
- Primary completionAug 2012
- Study completionOct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast NeoplasmsStudies of the same condition, open and under way.
- More trials run by Indiana UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Collaborators
- Breast Cancer Research Foundation, Geron Corporation
- Responsible party
- Sponsor
- Investigators
- Kathy Miller, MD, Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01265927
- Sponsor's protocol ID
- IUCRO-0314
- Other IDs
- 1010-05
- Status last verified
- Oct 2015
- First submitted
- 3 Dec 2010
- Last updated
- 27 Oct 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study Inhibiting Telomerase to Reverse Trastuzumab Resistance in HER2+ Breast Cancer
- ClinicalTrials.gov ID
- NCT01265927
- Acronym / sponsor ID
- IUCRO-0314
- Conditions
- Breast Neoplasms
- Keywords
- Breast Cancer, Breast Tumors, Cancer of Breast, Cancer of the Breast, Genes, HER-2, Genes, HER2
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Collaborators
- Breast Cancer Research Foundation, Geron Corporation
- Study start
- Jan 2011
- Primary completion
- Aug 2012 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 23 Dec 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A study to evaluate safety and biologic effects of giving GRN163L in combination with trastuzumab in patients diagnosed with HER2+ metastatic breast cancer that is resistant to therapy with trastuzumab.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| GRN163L + Trastuzumab | Experimental | Drug: GRN163L in combination with trastuzumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Males or females 18 years or older at the time of consent.
- ECOG performance status of 0-2 within 21 days of study registration.
- Histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease. NOTE: locally recurrent disease must not be amenable to surgery or radiation with curative intent.
- Measurable or evaluable disease according to RECIST v1.1 within 35 days prior to study registration.
- Disease must be amenable to biopsy (image-guided or via direct visualization of superficial lesions) with minimal risk to the patient. NOTE: Patients with disease limited to the lung and/or pleura are excluded.
Key exclusion criteria (13 listed)
- No Investigational therapy within 4 weeks of study registration
- No hormonal therapy within 2 weeks of study registration
- No cytotoxic chemotherapy within 2 weeks of study registration.
- No prior treatment with GRN163L
- No prior history of severe reaction to trastuzumab, as determined by the treating physician.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GRN163L in combination with trastuzumabAlso: Imetelstat Sodium, HerceptinGRN163L will be administered in escalating dose cohorts on Day 1 of each 21-day cycle prior to trastuzumab infusion. Trastuzumab will be a administered day 1 of each 21-day cycle after GRN163L. There will be a 30 minute observation period between the end of the GRN163L infusion and the beginning of the trastuzumab infusion. | Drug | GRN163L + Trastuzumab |
Primary outcome
Determine the dose-limiting toxicity of GRN163L in combination with trastuzumab in patients with refractory HER2+ metastatic disease
Time frame: End of Study
5 secondary outcomes
Measure the concentration of trastuzumab and GRN163L from blood samples immediately before and after infusion on day 1, weekly during cycle 1, and immediately prior to cycle 2
Time frame: Until cycle 2
Tumor biopsy and bone marrow aspirate assayed for telomerase activity prior to treatment and immediately prior to planned cycle 2
Time frame: Until cycle 2
Flow cytometry to compare cell cycle distribution in tumor and bone marrow prior to treatment and immediately prior to cycle 2.
Time frame: Until cycle 2
Tumor samples analyzed for activation of HER2 family signaling protein activation (phosphorylation) status prior to treatment and immediately prior to cycle 2.
Time frame: Until cycle 2
Determine objective response rate (ORR) and progression free survival (PFS) of GRN163L in combination with trastuzumab in this patient population
Time frame: End of Study
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kathy Miller, MD principal investigator
Indiana University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GRN163L in combination with trastuzumab in people with Breast Neoplasms, run by Indiana University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determine the dose-limiting toxicity of GRN163L in combination with trastuzumab in patients with refractory HER2+ metastatic disease (time frame: End of Study). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2015.